Major emphasis will be on development of the therapeutic applications of the cardiotonic ionophore X-537A and its available derivatives. Their ability to restore the cardiac contractility of surgically impaired hearts of dogs will be examined, both on a short term and long term basis. These studies will be supplimented by appropriate measurements of body chemistry, e.g. pyruvate-lactate levels, blood ionophore levels, renal function etc., in order to ascertain the composit effects on experimental subjects of X-537A which accompany its inotropic effects. In order to pinpoint the precise mechanism or combination of mechanisms underlying the pharmacological properties of X-537A, the effect of various metabolic pertubations, e.g. metabolic inhibitors, on tissue preparations including atrial strips, Purkinje fibers, perfused hearts will be studied. The effects of chronic administration of X-537A will also be evaluated. The physiological effects of other ionophores will be studied in order to assess their potential therapeutic applications. To supplement the metabolic studies we will continue to examine the molecular properties of X-537A and its derivatives with regard to the complexation and transport of cations by a variety of techniques including fluorescence, circular dichrosim and nuclear magnetic resonance.